Download Handout 25-27 - U of L Class Index

Mendelian genetic
(Lecture 25-27)
Gregor Mendel
An Austrian monk, Gregor Mendel, developed the fundamental principles that would become the
modern science of genetics. Mendel demonstrated that heritable properties are parceled out in discrete
units, independently inherited.
These eventually were termed genes.
Definitions
Character – is a heritable feature, such as flower color, that varies among individuals.
Each variant for a character, such as purple or white color for flowers, is called trait.
Garden pea
Mendel's experimental organism was a common self-pollinating garden pea (Pisum sativum).
The male parts of the flower are termed the anthers.
They produce pollen, which contains the male gametes (sperm).
The female parts of the flower are the stigma, style, and ovary.
The egg (female gamete) is produced in the ovary.
The process of pollination (the transfer of pollen from anther to stigma) occurs prior to the opening of the pea
flower.
The pollen grain grows a pollen tube which allows the sperm to travel through the stigma and style, eventually
reaching the ovary.
The ripened ovary wall becomes the fruit (in this case the pea pod).
Most flowers allow cross-pollination, which can be difficult to deal with in genetic studies if the male parent
plant is not known.
Since pea plants are self-pollinators, the genetics of the parent can be more easily understood.
Peas are also self-compatible, allowing self-fertilized embryos to develop as readily as out-fertilized embryos
– they are true-breeding.
Mendel reasoned an organism for genetic experiments should have:
1. A number of different traits that can be studied
2. Plant should be self-fertilizing and have a flower structure that limits accidental contact
3. Offspring of self-fertilized plants should be fully fertile.
Mendel tested all 34 varieties of peas available to him through seed dealers.
The garden peas were planted and studied for eight years.
Each character studied had two distinct forms, such as
tall or short plant height, or
smooth or wrinkled seeds.
Mendel's experiments used some 28,000 pea plants.
A genetic cross
To mate (hybridize) two varieties of pea plants, Mendel used an artist's brush to transfer sperm-bearing
pollen from one plant to the egg-bearing carpel of another.
In this case, the character of interest is flower color,
and the two varieties are purple-flowered and white-flowered.
Seed germination produces the first generation hybrids, which all have purple flowers.
The result is the same for the reciprocal cross, the transfer of pollen from purple flowers to white
flowers.
Three generations of pea
When F1 hybrids were allowed to self-pollinate, or when they were cross-pollinated with other F1
hybrids,
a 3:1 ratio of the two varieties occurred in the F2 generation.
An "X" sign symbolizes a genetic cross, or mating.
Alleles, contrasting versions of a gene
The gene for a particular inherited character, such as flower color in garden peas, resides at a specific locus
(position) on a certain chromosome.
Alleles are variants of that gene.
In this case, the flower-color gene exists in two versions: the allele for purple flowers and the allele for white
flowers.
The homologous pair of chromosomes represents an F1 hybrid, which inherited the allele for purple
flowers from one parent and the allele for white flowers from the other parent.
Mendel's work showed:
1.Each parent contributes one factor of each trait shown in offspring: alternative versions of genes
account for variations in inherited characters
2.The two members of each pair of factors segregate from each other during gamete formation.
3.The fully expressed allele is the dominant allele, the other that has no noticeable effect on the
organism’s appearance is the recessive allele
4.Males and females contribute equally to the traits in their offspring.
Mendel's law of segregation.
Mendel's model for monohybrid inheritance.
The purple-flower allele (P) is dominant, and the white-flower allele (p) is recessive.
Each true-breeding plant of the parental generation
has matching alleles, either PP (purple-flower parentals) or pp (white-flower parentals).
Gametes, symbolized with circles, each contain only one allele for the flower color gene.
Because the purple-flower allele is dominant, all these hybrids have purple flowers.
Segregation results in the production of the half of the P allele and the half of the p allele.
Random combination of these gametes results in the 3:1 ratio that Mendel observed in the F2 generation.
A Punnett square is a useful tool for showing all possible combinations of alleles in offspring.
Each square represents an equally probable product of fertilization.
Principle of segregation
Mendel crossed true-breeding smooth-seeded plants with wrinkled seeds-producing plants (60
fertilizations on 15 plants).
All resulting seeds were smooth.
The following year, Mendel planted these seeds and allowed them to self-fertilize.
He recovered 7324 seeds: 5474 smooth and 1850 wrinkled.
The parental generation is denoted as the P1 generation.
The offspring of the P1 generation are the F1 generation (first filial).
The self-fertilizing F1 generation produced the F2 generation (second filial).
Dominant traits were defined by Mendel as those which appeared in the F1 generation in crosses.
Recessives were those which "skipped" a generation, being expressed only when the dominant trait is
absent.
Mendel's plants exhibited complete dominance, in which the phenotypic expression of alleles was either
dominant or recessive, not "in between".
Mendel concluded that the traits under study were governed by discrete (separable) factors.
The factors were inherited in pairs, with each generation having a pair of trait factors.
We now refer to these trait factors as alleles.
Having traits inherited in pairs allows for the observed phenomena of traits "skipping" generations.
An organism that have a pair of identical alleles for a character is called homozygous.
An organism that have two different alleles for a gene are said to be heterozygous for that gene.
Because of dominance and recessiveness, an organism’s appearance does not always reveal its genetic
composition.
An organism appearance is called the phenotype.
Its genetic makeup is called genotype.
Summary of Mendel's Results:
1.The F1 offspring showed only one of the two parental traits, and always the same trait.
2.Results were always the same regardless of which parent donated the pollen (was male).
3.The trait not shown in the F1 reappeared in the F2 in about 25% of the offspring.
4.Traits remained unchanged when passed to offspring: they did not blend in any offspring but behaved
as separate units.
5.Reciprocal crosses showed each parent made an equal contribution to the offspring.
The testcross
A testcross is designed to reveal the genotype of an organism that exhibits a dominant trait.
Such an organism could be either homozygous for the dominant allele or heterozygous.
The most efficient way to determine the genotype is to cross the organism with an individual expressing
the recessive trait.
Since the genotype of the white-flowered parent must be homozygous, we can deduce the genotype of
the purple-flowered parent by observing the phenotypes of the offspring.
Dihybrid Crosses
A cross between true-breeding parent plants that differ in two characters produces F1 hybrids that are
heterozygous for both characters.
Yellow color (Y) and round shape (R) are dominant.
(a) If the two characters segregate dependently (together), the F1 hybrids can only produce the same two
classes of gametes that they received from the parents, and the F2 offspring will show a 3:1
phenotypic ratio.
(b) If the two characters segregate independently, four classes of gametes will be produced by the F1
generation, and there will be a 9:3:3:1 phenotypic ratio in the F2 generation.
Mendel's results supported this latter hypothesis, called independent assortment.
Methods, Results, and Conclusion
Mendel started with true-breeding plants that had smooth, yellow seeds and crossed them with truebreeding plants having green, wrinkled seeds.
All seeds in the F1 had smooth yellow seeds.
The F2 plants self-fertilized, and produced four phenotypes:
315 smooth yellow
108 smooth green
101 wrinkled yellow
32 wrinkled green
Mendel analyzed each trait for separate inheritance as if the other trait were not present.
The 3:1 ratio was seen separately and was in accordance with the Principle of Segregation.
The segregation of S and s alleles must have happened independently of the segregation of Y and y
alleles.
The chance of any gamete having a Y is 1/2; the chance of any one gamete having a S is 1/2.The chance
of a gamete having both Y and S is the product of their individual chances (or 1/2 X 1/2 = 1/4).
The chance of two gametes forming any given genotype is 1/4 X 1/4 (remember, the product of their
individual chances). Thus, the Punnett Square has 16 boxes. Since there are more possible combinations
to produce a smooth yellow phenotype (SSYY, SsYy, SsYY, and SSYy), that phenotype is more
common in the F2.
Principle of Independent Assortment
-that when gametes are formed, alleles assort independently.
Now (when DNA and chromosomes are known) we would interpret the Principle of Independent
Assortment as alleles of genes on different chromosomes are inherited independently during the
formation of gametes.
Segregation of alleles and fertilization as chance events
When a heterozygote (Pp) forms gametes, segregation of alleles is like the toss of a coin.
An ovum has a 50% chance of receiving the dominant allele and a 50% chance of receiving the
recessive allele.
The same odds apply to a sperm cell.
Like two separately tossed coins, segregation during sperm and ovum formation occurs as two
independent events.
To determine the probability that an individual offspring will inherit the dominant allele from both
parents, we multiply the probabilities of each required event: 1/2 x 1/2 = 1/4.
We can use the rule of multiplication to predict the probability for any genotype among offspring, as
long as we know the genotypes of the parents.
Genetic Terms
-Gene - a unit of inheritance that usually is directly responsible for one trait or character.
--Allele - an alternate form of a gene. Usually there are two alleles for every gene, sometimes as many a
three or four.
--Homozygous - when the two alleles are the same.
--Heterozygous - when the two alleles are different, in such cases the dominant allele is expressed.
-Dominant - a term applied to the trait (allele) that is expressed irregardless of the second allele.
-Recessive - a term applied to a trait that is only expressed when the second allele is the same (e.g. short
plants are homozygous for the recessive allele).
--Phenotype - the physical expression of the allelic composition for the trait under study.
--Genotype - the allelic composition of an organism.
--Punnett squares - probability diagram illustrating the possible offspring of a mating.
PART II
Finding the genes
Between 1884 (the year Mendel died) and 1888:
- details of mitosis and meiosis were reported;
-- the cell nucleus was identified as the location of the genetic material;
-- "qualities" were even proposed to be transmitted on chromosomes to daughter cells at mitosis.
-In 1903 Walter Sutton and Theodore Boveri formally proposed that chromosomes contain the genes.
The Chromosome Theory of Inheritance is one of the foundations of genetics and explains the physical
reality of Mendel's principles of inheritance.
The location of many genes (Mendel's factors) was determined by Thomas Hunt Morgan and his
coworkers in the early 1900's. Morgan's experimental organism was the fruit fly (Drosophila
melanogaster).
Fruit flies are ideal organisms for genetics, having a small size, ease of care, susceptibility to mutations, and short
(7-9 day) generation time. The role of chromosomes in determination of sex was deduced by Morgan from work
on fruit flies.
During Metaphase I, homologous chromosomes will line up.
A karyotype can be made by cutting and arranging photomicrographs of the homologous chromosomes thus
revealed at Metaphase I.
Two types of chromosome pairs occur.
Autosomes resemble each other in size and placement of the centromere, for example pairs of chromosome 21 are
the same size, while pairs of chromosome 9 are of a different size from pair 21.
Sex chromosomes may differ in their size, depending on the species of the organism they are from.
In humans and Drosophila, males have a smaller sex chromosome, termed the Y, and a larger one,
termed the X.
Males are thus XY, and are termed heterogametic.
Females are XX, and are termed homogametic.
In grasshoppers, which Sutton studied in discovering chromosomes, there is no Y, only the X
chromosome in males.
Females are XX, while males are denoted as XO.
Other organisms (notably birds, moths and butterflies) have males homogametic and females
heterogametic.
Males (if heterogametic) contribute either an X or Y to the offspring, while females contribute either X.
The male thus determines the sex of the offspring.
Morgan discovered a mutant eye color and attempted to use this mutant as a recessive to duplicate
Mendel's results.
He failed, instead of achieving a 3:1 F2 ratio the ratio was closer to 4:1 (red to white).
Most mutations are usually recessive, thus the appearance of the white mutant presented Morgan a
chance to test Mendel's ratios on animals.
The F1 generation also had no white eyed females.
Morgan hypothesized that the gene for eye color was only on the X chromosome,
specifically in that region of the X that had no corresponding region on the Y.
White eyed fruit flies were also more likely to die prior to adulthood, thus explaining the altered ratios.
Normally eyes are red, but a variant (white) eyed was detected and used in genetic study.
Cross a homozygous white eyed male with a homozygous red eyed female, and all the offspring have
red eyes.
Red is dominant over white.
However, cross a homozygous white eyed female with a red eyed male, and the unexpected results show
all the males have white eyes and all the females red eyes.
This can be explained if the eye color gene is on the X chromosome.
Sex-linkage
These experiments introduced the concept of sex-linkage,
the occurrence of genes on that part of the X that lack a corresponding location on the Y.
Sex-linked recessives (such as white eyes in fruit flies, hemophilia, baldness, and colorblindness in
humans) occur more commonly in males, since there is no chance of them being heterozygous.
Such a condition is termed hemizygous.
Characteristics of X-linked Traits
1. Phenotypic expression more common in males
2. Sons cannot inherit the trait from their fathers, but daughters can.
Sons inherit their Y chromosome from their father.
Only a few genes have been identified on the Y chromosome, among them the testis-determining factor
(TDF) that promotes development of the male phenotype.
Barr bodies are interpreted as inactivated X chromosomes in mammalian females.
Since females have two X chromosomes, the Lyon hypothesis suggests that one or the other X is
inactivated in each somatic (non-reproductive) cell during embryonic development.
Cells mitotically produced from these embryonic cells likewise have the same inactivated X
chromosome.
Incomplete dominance
Incomplete dominance is a condition when neither allele is dominant over the other.
The condition is recognized by the heterozygotes expressing an intermediate phenotype relative to the
parental phenotypes.
If a red snapdragons is crossed with a white flowered one, the progeny will all be pink.
When pink is crossed with pink, the progeny are 1 red, 2 pink, and 1 white.
Segregation of alleles into the gametes of the F1 plants results in an F2 generation with a 1:2:1 ratio for
both genotype and phenotype.
CR 5 allele for red flower color; CW 5 allele for white flower color.
Codominant alleles
Codominant alleles occur when rather than expressing an intermediate phenotype, the heterozygotes
express both homozygous phenotypes.
An example is in human ABO blood types, the heterozygote AB type manufactures antibodies to both A
and B types.
Blood Type A people manufacture only anti-B antibodies, while type B people make only anti-A
antibodies.
Codominant alleles are both expressed.
Heterozygotes for codominant alleles fully express both alleles.
Blood type AB individuals produce both A and B antigens.
Since neither A nor B is dominant over the other and they are both dominant over O they are said to be
codominant.
Many genes have more than two alleles (even though any one diploid individual can only have at most
two alleles for any gene), such as the ABO blood groups in humans, which are an example of multiple
alleles.
Multiple alleles
Multiple alleles result from different mutations of the same gene.
Coat color in rabbits is determined by four alleles.
Human ABO blood types are determined by alleles A, B, and O.
A and B are codominants which are both dominant over O.
The only possible genotype for a type O person is OO.
Type A people have either AA or AO genotypes.
Type B people have either BB or BO genotypes.
Type AB have only the AB (heterozygous) genotype.
The A and B alleles of gene I produce slightly different glycoproteins (antigens) that are on the surface
of each cell.
Homozygous A individuals have only the A antigen, homozygous B individuals have only the B antigen,
homozygous O individuals produce neither antigen, while a fourth phenotype (AB) produces both A and
B antigens.
Interactions among genes
While one gene may make only one protein, the effects of those proteins usually interact (for example
widow's peak may be masked by expression of the baldness gene).
Novel phenotypes often result from the interactions of two genes, as in the case of the comb in chickens.
The single comb is produced only by the rrpp genotype.
Rose comb (b) results from R_pp. (_ can be either R or r).
Pea comb (c) results from rrP_.
Walnut comb, a novel phenotype, is produced when the genotype has at least one dominant of each gene
(R_P_).
Epistasis
Epistasis is the term applied when one gene interferes with the expression of another (as in the
baldness/widow's peak mentioned earlier).
Bateson reported a different phenotypic ratio in sweet pea than could be explained by simple Mendelian
inheritance.
This ratio is 9:7 instead of the 9:3:3:1 one would expect of a dihybrid cross between heterozygotes.
Of the two genes (C and P), when either is homozygous recessive (cc or pp) that gene is epistatic to (or
hides) the other.
To get purple flowers one must have both C and P alleles present.
Matings between two black mice.
The parents are heterozygous for two genes, which assort independently of each other.
Thus our breeding experiment corresponds to a Mendelian F1 cross between dihybrids.
One gene determines whether the coat will be black (dominant, B) or brown (recessive, b).
The second gene controls whether or not pigment of any color will be deposited in the hair, with the allele for the
presence of color (C) dominant to the allele for the absence of color (c).
All offspring of the cc genotype are white (albino), regardless of the genotype for the black/brown genetic locus.
This epistatic relationship of the color gene to the black/brown gene results in an F2 phenotypic ratio of 9 black to
3 brown to 4 white.
Environment and gene expression
Phenotypes are always affected by their environment.
In buttercup (Ranunculus peltatus), leaves below water-level are finely divided and those above waterlevel are broad, floating, photosynthetic leaf-like leaves.
Siamese cats are darker on tExpression of phenotype is a result of interaction between genes and
environment.
Siamese cats and Himalayan rabbits both animals have dark colored fur on their extremities.
This is caused by an allele that controls pigment production being able only to function at the lower
temperatures of those extremities.
Environment determines the phenotypic pattern of expression
heir extremities, due to temperature effects on phenotypic expression.
Polygenic inheritance
Polygenic inheritance is a pattern responsible for many features that seem simple on the surface.
Many traits such as height, shape, weight, color, and metabolic rate are governed by the cumulative
effects of many genes.
Polygenic traits are not expressed as absolute or discrete characters, as was the case with Mendel's pea
plant traits.
Instead, polygenic traits are recognizable by their expression as a gradation of small differences (a
continuous variation).
The results form a bell shaped curve, with a mean value and extremes in either direction.
Height in humans is a polygenic trait, as is color in wheat kernels.
Height in humans is NOT discontinuous.
If you line up the entire class a continuum of variation is evident, with an average height and extremes in
variation (very short [vertically challenged?] and very tall [vertically enhanced]).
Traits showing continuous variation are usually controlled by the additive effects of two or more
separate gene pairs.
This is an example of polygenic inheritance.
The inheritance of EACH gene follows Mendelian rules.
Polygenic inheritance of skin color
Three separately inherited genes affect the darkness of skin.
For each gene, an allele for dark skin is incompletely dominant to an allele for light skin.
Thus, an individual who is heterozygous for all three genes (AaBbCc) has inherited three "units" of
darkness, indicated in this figure by the three dots in the small square.
An individual with the genotype AABbcc would also have a total of three units for dark skin.
Imagine a large number of matings between individuals who are heterozygous for all three genes.
Along the top of the graph are the variations that can occur among offspring.
The y-axis represents the fractions of these variations among offspring of such trihybrid matings.
Usually polygenic traits are distinguished by
1.Traits are usually quantified by measurement rather than counting.
2.Two or more gene pairs contribute to the phenotype.
3.Phenotypic expression of polygenic traits varies over a wide range.
Human polygenic traits include
1.Height
2.SLE (Lupus) (click here for an article about lupus and genetics)
3.Weight (click here for an article about obesity and genetics)
4.Eye Color (click here for an article about eye color)
5.Intelligence
6.Skin Color
7.Many forms of behavior
Pleiotropy
Pleiotropy is the effect of a single gene on more than one characteristic.
An example is the "frizzle-trait" in chickens.
The primary result of this gene is the production of defective feathers.
Secondary results are both good and bad; good include increased adaptation to warm temperatures, bad
include increased metabolic rate, decreased egg-laying, changes in heart, kidney and spleen.
Cats that are white with blue eyes are often deaf, white cats with a blue and an yellow-orange eye are
deaf on the side with the blue eye.
Sickle-cell anemia is a human disease originating in warm lowland tropical areas where malaria is
common.
Sickle-celled individuals suffer from a number of problems, all of which are pleiotropic effects of the
sickle-cell allele.
Genes and chromosomes
Linkage occurs when genes are on the same chromosome.
Remember that sex-linked genes are on the X chromosome, one of the sex chromosomes.
Linkage groups are invariably the same number as the pairs of homologous chromosomes an organism
possesses.
Recombination occurs when crossing-over has broken linkage groups, as in the case of the genes for
wing size and body color that Morgan studied.
Chromosome mapping was originally based on the frequencies of recombination between alleles.
Since mutations can be induced (by radiation or chemicals), Morgan and his coworkers were able to
cause new alleles to form by subjecting fruit flies to mutagens (agents of mutation, or mutation
generators).
Genes are located on specific regions of a certain chromosome termed the gene locus (plural: loci). A
gene therefore is a specific segment of the DNA molecule.
Chromosome abnormalities
include inversion, insertion, duplication, and deletion.
These are types of mutations.
Reading
CH. 14 (251-273) CH.15 (274-292)